A large new study is flipping the script on a long-held migraine assumption. Researchers found that plasma CGRP levels were actually lower in people with migraine compared to healthy adults — contradicting decades of belief that CGRP rises during attacks. The findings suggest that while CGRP remains a valid treatment target, it may not be a reliable blood-based biomarker for migraine.
For decades, clinicians and researchers assumed that calcitonin gene-related peptide (CGRP) levels in the blood would be elevated in people with migraine, given the peptide's central role in pain signaling. A new large-scale study is challenging that assumption — and the results may reshape how the field thinks about migraine biomarkers.
In a cross-sectional study of 588 adults with migraine and 147 healthy matched controls, researchers found that median plasma CGRP levels were actually lower in the migraine group (125 vs. 151 pmol/L). Crucially, levels didn't vary by migraine subtype, whether patients were mid-attack or between attacks, or whether they were on preventive therapy — including CGRP-targeting drugs.
Experts say the findings don't undermine CGRP as a therapeutic target, but they do highlight that a molecule can be mechanistically important without being a useful blood biomarker. CGRP likely acts in a highly localized microenvironment within the meninges, making peripheral blood measurements a poor proxy for what's happening at the trigeminal level.
Key Takeaways:
Why it matters: CGRP-targeting therapies are now a cornerstone of migraine prevention, but this study signals that blood CGRP testing has no reliable role in clinical decision-making — a critical message for HCPs managing migraine patients.
